tbuckley/cabot-search huggingface dataset:
Inflating Pressure and Not Expiratory Pressure Initiates Lung Injury at Birth in Preterm Lambs
Authors: David G. Tingay, Monique Fatmous, Kelly Kenna, Georgie Dowse, Ellen Douglas, Arun Sett, Elizabeth J. Perkins, Magdy Sourial, Prue M. Pereira-Fantini
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Inflation is essential for aeration at birth, but current inflating pressure settings are without an evidence base. Objectives: To determine the role of inflating pressure (ΔP), and its relationship with positive end-expiratory pressure (PEEP), in initiating early lung injury pathways in the preterm lamb lung. Methods: Preterm (124 to 127 d) steroid-exposed lambs (n = 45) were randomly allocated (8-10 per group) to 15 minutes of respiratory support with placental circulation and 20 or 30 cm H2O ΔP, with an initial high PEEP (maximum, 20 cm H2O) recruitment maneuver known to facilitate aeration (dynamic PEEP), and compared with dynamic PEEP with no ΔP or 30 cm H2O ΔP and low (4 cm H2O) PEEP. Lung mechanics and aeration were measured throughout. After an additional 30 minutes of apneic placental support, lung tissue and bronchoalveolar fluid were analyzed for regional lung injury, including proteomics. Measurements and Main Results: The 30 cm H2O ΔP and dynamic PEEP strategies resulted in quicker aeration and better compliance but higher tidal volumes (often >8 ml/kg, all P < 0.0001; mixed effects) and injury. ΔP 20 cm H2O with dynamic PEEP resulted in the same lung mechanics and aeration, but less energy transmission (tidal mechanical power), as ΔP 30 cm H2O with low PEEP. Dynamic PEEP without any tidal inflations resulted in the least lung injury. Use of any tidal inflating pressures altered metabolic, coagulation and complement protein pathways within the lung. Conclusions: Inflating pressure is essential for the preterm lung at birth, but it is also the primary mediator of lung injury. Greater focus is needed on strategies that identify the safest application of pressure in the delivery room.
Elevated Pulmonary Arterial Compliance Is Associated with Survival in Pulmonary Hypertension: Results from a Novel Network Medicine Analysis
Authors: Rui-Sheng Wang, Shi Huang, Stephen W. Waldo, Edward Hess, Madhura Gokhale, Shelsey W. Johnson, Katarina Zeder, Gaurav Choudhary, Jane A. Leopold, William M. Oldham, Gabor Kovacs, Matthew S. Freiberg, Ryan J. Tedford, Bradley A. Maron, Evan L. Brittain
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U.S. Veterans Affairs system (October 1, 2006-September 30, 2018). Network medicine framework was used to subgroup patients when considering an N of 79 variables per patient. The results informed outcome analyses in the discovery cohort and a sex-balanced validation right heart catheterization cohort from Vanderbilt University (September 24, 1998-December 20, 2013). Measurements and Main Results: From an N of 4,737 complete case patients with mPAP of 19-24 mm Hg, there were 21 distinct subgroups (network modules) (all-cause mortality range = 15.9-61.2% per module). Pulmonary arterial compliance (PAC) drove patient assignment to modules characterized by increased survival. When modeled continuously in patients with mPAP ⩾19 mm Hg (N = 37,744; age, 67.2 yr [range = 61.7-73.8 yr]; 96.7% male; median follow-up time, 1,236 d [range = 570-1,971 d]), the adjusted all-cause mortality hazard ratio was <1.0 beginning at PAC ⩾3.0 ml/mm Hg and decreased progressively to ∼7 ml/mm Hg. A protective association between PAC ⩾3.0 ml/mm Hg and mortality was also observed in the validation cohort (N = 1,514; age, 60.2 yr [range = 49.2-69.1 yr]; 48.0% male; median follow-up time, 2,485 d [range = 671-3,580 d]). The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P < 0.001) and 49% (95% confidence interval, 0.38-0.69; P < 0.001) improvements in survival were observed for PAC ⩾3.0 versus <3.0 ml/mm Hg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC ⩾3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.
In hypertension not treated with medications, renal denervation vs. sham reduced daytime ambulatory SBP at 2 mo
Authors: Joshua A. Samuels, Donald A. Molony
Journal: Annals of Internal Medicine (2023)

Source Citation Azizi M, Saxena M, Wang Y, et al; RADIANCE II Investigators and Collaborators. Endovascular ultrasound renal denervation to treat hypertension: the RADIANCE II randomized clinical trial. JAMA. 2023;329:651-661. 36853250
Effects of Implementation of a Supervised Walking Program in Veterans Affairs Hospitals
Authors: Susan N. Hastings, Karen M. Stechuchak, Ashley Choate, Courtney Harold Van Houtven, Kelli D. Allen, Virginia Wang, Cathleen Colón-Emeric, George L. Jackson, Teresa M. Damush, Cassie Meyer, Caitlin B. Kappler, Helen Hoenig, Nina Sperber, Cynthia J. Coffman
Journal: Annals of Internal Medicine (2023)

Background: In trials, hospital walking programs have been shown to improve functional ability after discharge, but little evidence exists about their effectiveness under routine practice conditions. Objective: To evaluate the effect of implementation of a supervised walking program known as STRIDE (AssiSTed EaRly MobIlity for HospitalizeD VEterans) on discharge to a skilled-nursing facility (SNF), length of stay (LOS), and inpatient falls. Design: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT03300336) Setting: 8 Veterans Affairs hospitals from 20 August 2017 to 19 August 2019. Patients: Analyses included hospitalizations involving patients aged 60 years or older who were community dwelling and admitted for 2 or more days to a participating medicine ward. Intervention: Hospitals were randomly assigned in 2 stratified blocks to a launch date for STRIDE. All hospitals received implementation support according to the Replicating Effective Programs framework. Measurements: The prespecified primary outcomes were discharge to a SNF and hospital LOS, and having 1 or more inpatient falls was exploratory. Generalized linear mixed models were fit to account for clustering of patients within hospitals and included patient-level covariates. Results: Patients in pre-STRIDE time periods (n = 6722) were similar to post-STRIDE time periods (n = 6141). The proportion of patients with any documented walk during a potentially eligible hospitalization ranged from 0.6% to 22.7% per hospital. The estimated rates of discharge to a SNF were 13% pre-STRIDE and 8% post-STRIDE. In adjusted models, odds of discharge to a SNF were lower among eligible patients hospitalized in post-STRIDE time periods (odds ratio [OR], 0.6 [95% CI, 0.5 to 0.8]) compared with pre-STRIDE. Findings were robust to sensitivity analyses. There were no differences in LOS (rate ratio, 1.0 [CI, 0.9 to 1.1]) or having an inpatient fall (OR, 0.8 [CI, 0.5 to 1.1]). Limitation: Direct program reach was low. Conclusion: Although the reach was limited and variable, hospitalizations occurring during the STRIDE hospital walking program implementation period had lower odds of discharge to a SNF, with no change in hospital LOS or inpatient falls. Primary Funding Source: U.S. Department of Veterans Affairs Quality Enhancement Research Initiative (Optimizing Function and Independence QUERI).
Diagnostic Strategies for the Assessment of Suspected Stable Coronary Artery Disease
Authors: Andrea Zito, Mattia Galli, Giuseppe Biondi-Zoccai, Antonio Abbate, Pamela S. Douglas, Giuseppe Princi, Domenico D’Amario, Cristina Aurigemma, Enrico Romagnoli, Carlo Trani, Francesco Burzotta
Journal: Annals of Internal Medicine (2023)

Background: There is uncertainty about which diagnostic strategy for detecting coronary artery disease (CAD) provides better outcomes. Purpose: To compare the effect on clinical management and subsequent health effects of alternative diagnostic strategies for the initial assessment of suspected stable CAD. Data Sources: PubMed, Embase, and Cochrane Central Register of Controlled Trials. Study Selection: Randomized clinical trials comparing diagnostic strategies for CAD detection among patients with symptoms suggestive of stable CAD. Data Extraction: Three investigators independently extracted study data. Data Synthesis: The strongest available evidence was for 3 of the 6 comparisons: coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) (4 trials), CCTA versus exercise electrocardiography (ECG) (2 trials), and CCTA versus stress single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) (5 trials). Compared with direct ICA referral, CCTA was associated with no difference in cardiovascular death and myocardial infarction (relative risk [RR], 0.84 [95% CI, 0.52 to 1.35]; low certainty) but less index ICA (RR, 0.23 [CI, 0.22 to 0.25]; high certainty) and index revascularization (RR, 0.71 [CI, 0.63 to 0.80]; moderate certainty). Moreover, CCTA was associated with a reduction in cardiovascular death and myocardial infarction compared with exercise ECG (RR, 0.66 [CI, 0.44 to 0.99]; moderate certainty) and SPECT-MPI (RR, 0.64 [CI, 0.45 to 0.90]; high certainty). However, CCTA was associated with more index revascularization (RR, 1.78 [CI, 1.33 to 2.38]; moderate certainty) but less downstream testing (RR, 0.56 [CI, 0.45 to 0.71]; very low certainty) than exercise ECG. Low-certainty evidence compared SPECT-MPI versus exercise ECG (2 trials), SPECT-MPI versus stress cardiovascular magnetic resonance imaging (1 trial), and stress echocardiography versus exercise ECG (1 trial). Limitation: Most comparisons primarily rely on a single study, many studies were underpowered to detect potential differences in direct health outcomes, and individual patient data were lacking. Conclusion: For the initial assessment of patients with suspected stable CAD, CCTA was associated with similar health effects to direct ICA referral, and with a health benefit compared with exercise ECG and SPECT-MPI. Further research is needed to better assess the relative performance of each diagnostic strategy. Primary Funding Source: None. (PROSPERO: CRD42022329635).
In severe tricuspid regurgitation, tricuspid TEER improved QoL more than medical therapy at 1 y
Authors: Alan Zajarias, Richard G. Bach
Journal: Annals of Internal Medicine (2023)

Source Citation Sorajja P, Whisenant B, Hamid N, et al; TRILUMINATE Pivotal Investigators. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med. 4 Mar 2023. [Epub ahead of print]. 36876753
Intrathecal delivery of Macromolecules: Clinical status and emerging technologies
Authors: Rana Ajeeb, John R. Clegg
Journal: Advanced Drug Delivery Reviews (2023)

The proximity and association of cerebrospinal fluid (CSF) and the intrathecal (IT) space with deep targets in the central nervous system (CNS) parenchyma makes IT injection an attractive route of administration for brain drug delivery. However, the extent to which intrathecally administered macromolecules are effective in treating neurological diseases is a question of both clinical debate and technological interest. We present the biological, chemical, and physical properties of the intrathecal space that are relevant to drug absorption, distribution, metabolism, and elimination from CSF. We then analyze the evolution of IT drug delivery in clinical trials over the last 20 years. Our analysis revealed that the percentage of clinical trials assessing IT delivery for the delivery of biologics (i.e., macromolecules, cells) for treatment of chronic conditions (e.g., neurodegeneration, cancer, and metabolic diseases) has steadily increased. Clinical trials exploring cell or macromolecular delivery within the IT space have not evaluated engineering technologies, such as depots, particles, or other delivery systems. Recent pre-clinical studies have evaluated IT macromolecule delivery in small animals, postulating that delivery efficacy can be assisted by external medical devices, micro- or nanoparticles, bulk biomaterials, and viral vectors. Further studies are necessary to evaluate the extent to which engineering technologies and IT administration improve CNS targeting and therapeutic outcome.
Opportunities and challenges of leveraging COVID-19 vaccine innovation and technologies for developing sustainable vaccine manufacturing capabilities in Africa
Authors: Bavesh D Kana, Patrick Arbuthnot, Benjamin K Botwe, Yahya E Choonara, Fatima Hassan, Hechmi Louzir, Precious Matsoso, Penny L Moore, Apollo Muhairwe, Kubendran Naidoo, Margareth Ndomondo-Sigonda, Shabir A Madhi
Journal: The Lancet Infectious Diseases (2023)
Ovarian Metastasis From Diffuse Epithelioid Malignant Mesothelioma Revealed by 18F-FDG PET/CT
Authors: Guozhu Hou, Yujing Jin, Pan Peng, Rong Zheng
Journal: Clinical Nuclear Medicine (2023)

Abstract Diffuse epithelioid malignant mesothelioma (MM) with metastasis to the ovary is rare. We reported FDG PET/CT findings in a 39-year-old woman with ovarian metastasis from diffuse epithelioid MM. The ultrasound findings at the external hospital revealed multiple masses in the hepatic hilus. FDG PET/CT examination was recommended to evaluate the nature of the lesions. It showed that 2 hypodense lesions in the perihepatic space had intense activity, and there was an additional FDG lesion in the right ovary, which was later confirmed as diffuse epithelioid MM with ovarian metastasis by pathological examination.
Genotype-guided drug prescribing vs. usual care reduced clinically relevant adverse drug reactions at 12 wk
Authors: Anne M. Holbrook
Journal: Annals of Internal Medicine (2023)

Source Citation Swen JJ, van der Wouden CH, Manson LE, et al; Ubiquitous Pharmacogenetics Consortium. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401:347-356. 36739136
Residual insulin secretion in individuals with type 1 diabetes in Finland: longitudinal and cross-sectional analyses
Authors: Minna Harsunen, Jani Haukka, Valma Harjutsalo, Nina Mars, Anna Syreeni, Taina Härkönen, Annemari Käräjämäki, Jorma Ilonen, Mikael Knip, Niina Sandholm, Päivi Johanna Miettinen, Per-Henrik Groop, Tiinamaija Tuomi
Journal: The Lancet Diabetes & Endocrinology (2023)
Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets
Authors: Katrien Benhalima, Kaat Beunen, Sarah E Siegelaar, Rebecca Painter, Helen R Murphy, Denice S Feig, Lois E Donovan, Sarit Polsky, Elizabeth Buschur, Carol J Levy, Yogish C Kudva, Tadej Battelino, Lene Ringholm, Elisabeth R Mathiesen, Chantal Mathieu
Journal: The Lancet Diabetes & Endocrinology (2023)
Neutralising immunity to omicron sublineages BQ.1.1, XBB, and XBB.1.5 in healthy adults is boosted by bivalent BA.1-containing mRNA vaccination and previous Omicron infection
Authors: Edward J Carr, Mary Y Wu, Joshua Gahir, Ruth Harvey, Hermaleigh Townsley, Chris Bailey, Ashley S Fowler, Giulia Dowgier, Agnieszka Hobbs, Lou Herman, Martina Ragno, Murad Miah, Phillip Bawumia, Callie Smith, Mauro Miranda, Harriet V Mears, Lorin Adams, Emine Haptipoglu, Nicola O’Reilly, Scott Warchal, Chelsea Sawyer, Karen Ambrose, Gavin Kelly, Rupert Beale, Padmasayee Papineni, Tumena Corrah, Richard Gilson, Steve Gamblin, George Kassiotis, Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi, David LV Bauer, Emma C Wall
Journal: The Lancet Infectious Diseases (2023)
Issue Information
Authors: Daniel Solomon, Richard Bucala, New Haven, Mariana Kaplan, Peter Nigrovic, Boston Co, Karen Costenbader, David Felson, Richard Loeser, Hill Social, Paul Sufka, Amr Sawalha, Susan Boackle, Aileen Davis, Daniel Horton, New Brunswick, Bharat Kumar, Iowa City, Brandon Law, Michelle Ormseth, Suraj Rajasimhan, Kimberly Murphy, Lesley Allen, Virginia Brian, T Robinson, Stefanie Mckain, Georgia Rasa, G Hamilton, Florida Reynolds, Georgia Jenson, Marta Alarcón-Riquelme, Heather Allore, Neal Basu, Edward Behrens, Bryce Binstadt, Nunzio Bottini, San Diego, John Carrino, New York, Andrew Cope, Adam Croft, Nicola Dalbeth, Brian Feldman, Richard Furie, Great Neck, J Kahlenberg, Ann Arbor, Benjamin Leder, Yvonne Lee, Katherine Liao, Bing Lu, Stephen Messier, Winston-Salem Rachel, E Miller, Janet Pope, Lisa Rider, Christopher Ritchlin, Rochester Robinson, Carla Scanzello, Georg Schett, Sakae Tanaka, Maria Trojanowska, Betty Tsao, Fredrick Wigley, Edith Williams, Ayaz Aghayev, Joshua Baker, Bonnie Bermas, Jamie Collins, Kristen Demoruelle, Denver Denton, Anisha Dua, John Fitzgerald, Angeles Henderson, Monique Hinchcliff, Hui-Chen Hsu, Mohit Kapoor, Seoyoung Kim, Vasileios Kyttaris, Carl Langefeld, Winston-Salem Dennis Mcgonagle, Julie Paik, Julie Zikherman, Francisco American, Douglas White, La Crosse, Deborah Desir, Carol Langford, Steven Echard
Journal: Arthritis & Rheumatology (2023)
Unexpected Origin of Lung Metastases
Authors: Wenlan Zhou, Hubing Wu
Journal: Clinical Nuclear Medicine (2023)

Abstract A 49-year-old woman was referred to our hospital due to suspected lung metastases for 1 month. She had a history of thyroid micropapillary carcinoma and uterine leiomyomas. An 18 F-FDG PET/CT scan, which was performed to search the source of the presumed metastasis of the disease, showed multiple lung metastases and 2 18 F-FDG–avid foci in the thyroid and colon. Biopsy of lung and resection of colon lesions were then performed, and the disease was finally identified to be rare primary colon leiomyosarcoma with multiple lung metastases.
68Ga-FAPI-04 PET/MRI in a Case of Tuberous Sclerosis Complex With Extrarenal Retroperitoneal Angiomyolipoma
Authors: Aisheng Dong, Bo Yang, Qinqin Yang, Chao Cheng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2023)

Extrarenal retroperitoneal angiomyolipomas are rare benign tumors that may mimic other benign or malignant retroperitoneal tumors. We describe 68 Ga-FAPI-04 PET/MRI findings in a case of tuberous sclerosis complex with an extrarenal retroperitoneal angiomyolipoma and multiple angiomyolipomas involving bilateral kidneys. The extrarenal retroperitoneal angiomyolipoma and most of the renal angiomyolipomas were 68 Ga-FAPI-04-avid. One left renal angiomyolipoma with extensive hemorrhage and fibrosis had no significant 68 Ga-FAPI-04 uptake. Angiomyolipoma should be included in the differential diagnosis of FAPI-avid renal or extrarenal retroperitoneal lesions.
In TB, an 8-wk, 5-drug regimen was noninferior to a standard 24-wk, 4-drug regimen for clinical outcomes at 96 wk
Authors: Henry S. Sacks
Journal: Annals of Internal Medicine (2023)

ACP Journal ClubJune 2023In TB, an 8-wk, 5-drug regimen was noninferior to a standard 24-wk, 4-drug regimen for clinical outcomes at 96 wkHenry S. Sacks , PhD, MDHenry S. Sacks , PhD, MDIcahn School of Medicine at Mount Sinai, New York, New York, USA (H.S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J23-0036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationPaton NI, Cousins C, Suresh C, et al; TRUNCATE-TB Trial Team. Treatment strategy for rifampin-susceptible tuberculosis. N Engl J Med. 2023;388:873-887. https://pubmed.ncbi.nlm.nih.gov/36808186Clinical Impact RatingsGIM/FP/GP: Infectious Disease: Pulmonology: References1. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63:e147-e195. [PMID: 27516382] Google Scholar2. Edwards BD, Field SK. The struggle to end a millennia-long pandemic: novel candidate and repurposed drugs for the treatment of tuberculosis. Drugs. 2022;82:1695-1715. [PMID: 36479687] Google Scholar3. Dartois V, Rubin EJ. Shortening tuberculosis treatment—a strategic retreat [Editorial]. N Engl J Med. 2023;388:939-941. [PMID: 36807402] Google Scholar Author, Article, and Disclosure InformationAuthors: Henry S. Sacks, PhD, MDAffiliations: Icahn School of Medicine at Mount Sinai, New York, New York, USA (H.S.S.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0036.This article was published at Annals.org on 6 June 2023.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2023Volume 176, Issue 6Page: JC64KeywordsDrugsIsoniazidMultidrug resistanceNucleic acidsRandomized trialsSerious adverse eventsThoraxToxicityTuberculosis ePublished: 6 June 2023 Issue Published: June 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Oral Microbiota and Pediatric Asthma Phenotype: A New Window for Biomarkers?
Authors: Elodie Ghedin, Yvonne J. Huang
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Oral Microbiota and Pediatric Asthma Phenotype: A New Window for Biomarkers?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk
Authors: Rodolfo A. Estrada
Journal: Annals of Internal Medicine (2023)

Source Citation Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388:1478-1490. 36877098
Effectiveness of COVID-19 Treatment With Nirmatrelvir–Ritonavir or Molnupiravir Among U.S. Veterans: Target Trial Emulation Studies With One-Month and Six-Month Outcomes
Authors: Kristina L. Bajema, Kristin Berry, Elani Streja, Nallakkandi Rajeevan, Yuli Li, Pradeep Mutalik, Lei Yan, Francesca Cunningham, Denise M. Hynes, Mazhgan Rowneki, Amy Bohnert, Edward J. Boyko, Theodore J. Iwashyna, Matthew L. Maciejewski, Thomas F. Osborne, Elizabeth M. Viglianti, Mihaela Aslan, Grant D. Huang, George N. Ioannou
Journal: Annals of Internal Medicine (2023)

Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited.